文献：

Cyclovirobuxine D Brain-Targeted Liposomes Improve Cerebral Ischemia-Reperfusion Injury via Anti-Oxidant Stress and Activating Autophagy

文献链接：

https://www.ingentaconnect.com/contentone/asp/jbn/2022/00000018/00000004/art00020

作者：

Fang Yang ， Lingzhi Ren, Tuo Liu , Xiangyi Lu , Chang Liu , Yang Yu , Zhilian Chen , Yongling Long

相关产品：

DSPE-PEG （磷脂-聚乙二醇）

原文摘要：

One of the main issues faced by nervous system diseases is that drugs are difficult to enter the brain. The previous study suggested that Cyclovirobuxine D (CVBD) encapsulated in Angiopep-conjugated Polysorbate 80-Coated Liposomes showed a better brain targeting by intranasal administration. Therefore, this study concentrated on the protection and mechanism of CVBD brain-targeted liposomes in treating CIRI. Middle cerebral artery occlusion-reperfusion induced CIRI model rats to explore the protective effect of CVBD brain-targeted liposome on CIRI. Moreover, the protective effect of CVBD liposomes on OGD/R-injured HT22 cells was examined by cell fusion degree, cell proliferation curve and cell viability. OGD/R-injured HT22 cell was infected by mRFP-GFP-LC3 adenovirus. The autophagosome and autophagy flow were observed by laser confocal microscopy, and autophagy-related protein expressions were analyzed by Western blot. The classic autophagy inhibitor, chloroquine, was used to explore the autophagy-regulatedmechanism of CVBD brain-targeted liposomes in treating CIRI. CVBD liposomes increased cell viability and decreased ROS level, improved oxidative stress protein expressions and activated autophagy in vitro. Furthermore, CVBD liposomes reversed the decrease of cell viability, increase of ROS level, and reduction of protein expressions associated with anti-oxidative stress and autophagy induced by chloroquine. Collectively, CVBD liposomes inhibited CIRI via regulating oxidative stress and enhancing autophagy level in vivo and in vitro.   

DSPE-PEG 2000：DSPE - PEG 是由 1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷酸乙醇胺（DSPE）和聚乙二醇（PEG）组成的化合物。DSPE 是一种磷脂，具有典型的磷脂结构，包含一个甘油骨架，连接着两个硬脂酸（一种长链脂肪酸）和一个磷酸乙醇胺头部基团。这种结构使得 DSPE 具有亲脂性。PEG 是一种线性聚合物，由多个乙二醇单元重复连接而成，具有良好的亲水性。2000表示其分子量。基于DSPE-PEG 2000的性能，CVBD 脂质体的合成如下：

图：DSPE-PEG结构式

首先，将磷脂（含有 DSPE - PEG 2000 的磷脂混合物）和 CVBD溶解在有机溶剂（如氯仿或二氯甲烷）中，形成均匀的有机溶液。然后，在减压条件下（如旋转蒸发仪）除去有机溶剂，使磷脂和 CVBD 在容器壁上形成一层薄膜。接着，加入适当的缓冲液（如磷酸盐缓冲液），在高于磷脂相变温度的条件下进行水化，使磷脂薄膜重新分散形成脂质体。在这个过程中，DSPE - PEG 2000 随着其他磷脂一起形成脂质双层结构，包裹 CVBD 成分，从而形成 CVBD 脂质体。

结论：

该文献成功制备出基于DSPE-PEG 2000合成的CVBD 脂质体。CVBD 脂质体能够增加细胞活力并降低 ROS 水平，改善氧化应激蛋白表达和激活自噬体外。此外，CVBD 脂质体逆转了与氯喹诱导的抗氧化应激和自噬相关的细胞活力降低、ROS 水平升高和蛋白质表达降低。总之，CVBD 脂质体能够通过调节氧化应激和提高体内和体外自噬水平来抑制 CIRI 。